Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation for the treatment of childhood and adolescent Hodgkin disease

J Pediatr Hematol Oncol. 2001 Feb;23(2):84-8. doi: 10.1097/00043426-200102000-00003.

Abstract

Purpose: The outlook for children and adolescents with Hodgkin disease (HD) is excellent with combined modality therapy. However, the long-term toxicities of multiagent therapy and radiation therapy remain of concern for these patients with curable disease. In an attempt to reduce long-term toxicities while preserving excellent cure rates, we developed a combined-modality protocol using a modified seven-drug hybrid and low-dose (2,000 cGy) involved field radiation therapy (RT). The hybrid used cumulative doses of alkylating agents and anthracyclines that were lower than those used in previous four-drug regimens and substituted a less leukemogenic agent, cyclophosphamide, for nitrogen mustard.

Patients and methods: From 1991 through 1994 a cyclophosphamide, vincristine, procarbazine, and prednisone/adriamycin, bleomycin, and vinblastine hybrid was used to treat 29 patients with HD. Median age was 12 years (range 6-16 yrs). Patients who were postpubertal with early stage disease as determined by surgical staging were excluded. Treatment consisted of four cycles of therapy for stages I and IIA, six cycles for stages IIB and III, and eight cycles for stage IV. Twenty-two patients also received low-dose RT to areas of bulky disease.

Results: Twenty-eight patients (97%) had a complete response to chemotherapy. Five patients experienced relapse; two died from disease 27 and 29 months after initial diagnosis; three received additional therapy and are alive with no evidence of disease. Follow-up for all other patients is a median of 56 months (range 24-78 mos) from cessation of therapy and all have remained disease-free. At 5 years follow-up, actuarial disease-free survival is 82%, and the overall survival is 93%. There have been no clinically significant cardiac or pulmonary toxicities and no secondary malignancies.

Conclusions: This therapy has resulted in 5-year overall survival and disease-free survival rates similar to regimens using higher doses of alkylating agents, anthracyclines, and radiation. Longer follow-up will be necessary to fully evaluate disease-free survival, organ damage, and quality of life.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Child
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / mortality
  • Hodgkin Disease / pathology
  • Hodgkin Disease / radiotherapy
  • Humans
  • Hypothyroidism / etiology
  • Male
  • Neoplasm Staging
  • Neoplasms, Second Primary / etiology
  • Neoplasms, Second Primary / prevention & control
  • Neutropenia / chemically induced
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Procarbazine / administration & dosage
  • Procarbazine / adverse effects
  • Puberty, Delayed / etiology
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant / adverse effects
  • Remission Induction
  • Survival Rate
  • Thrombocytopenia / chemically induced
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Bleomycin
  • Procarbazine
  • Vincristine
  • Vinblastine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CVPPABO protocol